Pyrazolecarboxamide and pyrazolethioamide as fungicide

ABSTRACT

Novel pyraole derivatives of formula (I), wherein: X is oxygen or sufu, R 1  is C 1 –C 3 alkyl, C 1 –C 3 haloalkyl, C 1 –C 3 alkoxy-C 1 –C 3 alkyl or C 1 –C 3 haloalkoxy-C 1 –C 3 alkyl; R 2  is C 1 –C 3 haloalkyl; and R 3  is halogen. The novel compounds have plant-protective properties and are suitable for protecting plants against infestations by phytopathogenic microorganisms.

The present invention relates to novel pyrazolecarboxamides orpyrazolethioamides which have microbicidal activity, in particularfungicidal activity. The invention also relates to the preparation ofthese substances, to agrochemical compositions which comprise at leastone of the novel compounds as active ingredient, to the preparation ofthe compositions mentioned and to the use of the active ingredients orcompositions in agriculture and horticulture for controlling orpreventing infestation of plants by phytopathogenic microorganisms,preferably fungi.

The pyrazolecarboxamides of the present invention have the generalformula I

whereinX is oxygen or sulfur;R₁ is C₁–C₃alkyl, C₁–C₃haloalkyl, C₁–C₃alkoxy-C₁–C₃alkyl orC₁–C₃haloalkoxy-C₁–C₃alkyl;R₂ is C₁, —C₃haloalkyl; andR₃ is halogen.

Surprisingly, it has now been found that the compounds of formula Iexhibit improved biological properties which render them more suitablefor the practical use in agriculture and horticulture.

Where asymmetrical carbon atoms are present in the compounds of formulaI, these compounds are in optically active form. The invention relatesto the pure isomers, such as enantiomers and diastereomers, as well asto all possible mixtures of isomers, e.g. mixtures of diastereomers,racemates or mixture of racemates.

Within the present specification alkyl denotes methyl, ethyl, n-propyland isopropyl. Alkyl as part of other radicals such as alkoxyalkyl,haloalkyl or haloalkoxyalkyl is understood in an analogous way. Halogenwill be understood generally as meaning fluoro, chloro, bromo or iodo.Fluoro, chloro or bromo are preferred meanings. Halogen as part of otherradicals such as haloalkyl or haloalkoxyalkyl is understood in ananalogous way. Typical alkoxyalkyl radicals include methoxymethyl,ethoxymethyl, propoxymethyl, methoxyethyl, ethoxyethyl andmethoxypropyl. Typical haloalkoxyalkyl radicals includefluoromethoxymethyl, difluoromethoxymethyl, trifluoromethoxymethyl,2,2,2-trifluoroethoxymethyl, 3-chloropro-poxymethyl,2,2,3,3,3-pentafluoropropoxymethyl, 2,2,2-trifluoroethxyethyl andtrifluoromethoxypropyl.

Within the group of compounds of formula I those compounds are preferredwherein X is oxygen (subgroup A).

Another group of compounds of formula I are those wherein X is sulfur(subgroup B).

Within the subgroups A and B those compounds are preferred wherein

R₁ is C₁–C₃alkyl; or

R₁ is C₁–C₃alkoxy-C₁–C₃alkyl or C₁–C₃haloalkoxy-C₁–C₃alkyl;

R₂ is C₁–C₃haloalkyl; or

R₂ is CF₃, CF₂H, CFH₂, CF₂C₁, CF₂CF₃, CCl₃, CH₂CF₃, CH₂CCl₃ orCF₂CF₂CF₃; and

R₃ is fluoro, chloro or bromo (subgroups AC and BD).

Within the subgroup A are those compounds preferred wherein

R₁ is C₁–C₃alkyl;

R₂ is C₁–C₃haloalkyl; and

R₃ is fluoro, chloro or bromo (subgroup A1).

Within the scope of subgroup A1 those compounds of formula I areparticularly preferred, wherein

R₂ is CF₃, CF₂H, CFH₂, CF₂C₁, CF₂CF₃, CCl₃, CH₂CF₃, CH₂CCl₃ or CF₂CF₂CF₃(subgroup A2).

Another preferred embodiment of compounds of formula I are those withinsubgroup A, wherein

R₁ is C₁–C₃haloalkyl;

R₂ is C₁–C₃haloalkyl; and

R₃ is fluoro, chloro or bromo (subgroup A3).

A preferred embodiment of compounds of formula I are those withinsubgroup A, wherein

R₁ is C₁–C₃alkoxy-C₁–C₃alkyl or C₁–C₄haloalkoxy-C₁–C₃alkyl;

R₂ is C₁–C₃haloalkyl; and

R₃ is fluoro, chloro or bromo (subgroup A4).

Within the scope of subgroup B those compounds of formula I arepreferred, wherein

R₁ is C₁–C₃alkyl;

R₂ is C₁–C₃haloalkyl; and

R₃ is fluoro, chloro or bromo (subgroup B1).

A special group of compounds of formula I within the scope of subgroupB1 are those, wherein

R₂ is CF₃, CF₂H, CFH₂, CF₂C₁, CF₂CF₃, CCl₃, CH₂CF₃, CH₂CCl₃ or CF₂CF₂CF₃(subgroup B2).

Within the scope of subgroup B another preferred embodiment of compoundsof formula I are those, wherein

R₁ is C₁–C₃haloalkyl;

R₂ is C₁–C₃haloalkyl; and

R₃ is fluoro, chloro or bromo (subgroup B3).

A preferred embodiment of compounds of formula I are those withinsubgroup B, wherein

R₁ is C₁–C₃alkoxy-C₁–C₃alkyl or C₁–C₃haloalkoxy-C₁–C₃alkyl;

R₂ is C₁–C₃haloalkyl; and

R₃ is fluoro, chloro or bromo (subgroup B4).

Most preferred within the scope of subgroup AC are those compoundswherein

R₁ is CH₃ or CH₂OCH₃; and

R₂ is CF₃, CF₂H or CFH₂ (subgroup C).

Particularly preferred within the scope of subgroup C are thosecompounds wherein

R₁ is CH₃; and

R₂ is CF₃ (subgroup C1).

Another preferred embodiment within the scope of subgroup BD are thosecompounds wherein

R₁ is CH₃ or CH₂OCH₃; and

R₂ is CF₃, CF₂H or CFH₂ (subgroup D).

Within the scope of subgroup D are particularly preferred thosecompounds wherein

R₁ is CH₃; and

R₂ is CF₃ (subgroup D1).

The compounds according to formula I may be prepared according to thefollowing reaction in scheme 1.

The pyrazole carboxylic acid II reacts with an activating agent suchthionyl chloride, phosphorous pentachloride or oxalyl chloride to givethe corresponding acid chloride in the presence of a solvent at atemperature between 0° C. and reflux temperature and a reaction time of30 minutes to 24 hours. Representative solvents are toluene, benzene,xylene, hexane, cyclohexane chloroform or methylenechloride. Theobtained acyl chloride III are normally not isolated. The newcarboxamides of formula Ia are preferably obtained by reacting theactivated carboxylic acid of formula III with an aromatic amine offormula IV in the presence of a solvent like toluene, benzene, xylene,hexane, cyclohexane chloroform or methylenechloride and in the presenceof an acid binding agent like triethylamine, Hünig base, sodiumcarbonate, potassium carbonate or sodium hydrogencarbonate at atemperature between 0° C. and reflux temperature. The pyrazolethioamideslb are obtained by reacting the pyrazolecarboxamides la withphosphorpentasulfid or Lawesson-reagent in a solvent like dioxane,tetrahydrofurane or toluene at a temperature between 0° C. and refluxtemperature. Preferably the entire reaction sequence of scheme 1 isconducted as a single-vessel reaction.

The compounds according to the formula I may also be prepared accordingto the following reaction in scheme 1A.

The “in situ” prepared pyrazole carboxylic acid chloride III reacts withan ortho-halosubstituted phenylamine in the presence of a solvent liketoluene, benzene, xylene, hexane, cyclohexane, THF, chloroform ormethylenechloride and in the presence of a base like sodium carbonate,sodium hydrogencarbonate, potassium carbonate, Hünig base, triethylamineor pyridine at a temperature between 0° C. and reflux temperature. Theobtained pyrazolecarboxamide of formula Va reacts with the p-substitutedphenyl boronic acid (VI) in the presence of a Pd-catalyst likePd(P(phenyl)₃)₄, Pd(P(phenyl₃)Cl₂, PdCl₂dppb, Pd₂(dba)₃, Pd(OAc)₂,PdOAc₂/(o-tolyl)₃P, Pd(OAc)₂/dppf, Pd(PhCN)₂Cl₂/Ph₃As, Pd(CH₃CN)₂Cl₂,Pd₂(dba)₃/P(tert.butyl)₃, Pd(OAc)₂/P(tert.butyl)₂biphenyl,Pd(OAc)₂/TPPTS, Pd(OAc)₂/PCy₃, Pd(OAc)₂/P(O-i—Pr)₃,Pd(OAc)₂/2-dimethylamino-2′-dicyclohexylphosphinobiphenyl,Pd(OAc)₂/2-dimethylamino-2′-ditert.butylphosphinobiphenyl,Pd(OAc)₂/(o-biphenyl)P(cyclohexyl)₂ in a solvent like1,2-dimethoxyethane/water, DMF, DMA, THF/water, dioxane/water, benzene,toluene, xylene and others and a base like sodium carbonate, sodiumhydrogencarbonate, potassium carbonate, cesium carbonate, potassiumphosphate, triethylamine, sodium hydroxide, sodium ethylate, sodiumtert.butylate, silver oxide, barium carbonate, potassium fluoride orcesium fluoride at a temperature between 0° C. and reflux temperature.

The pyrazolethioamide lb is obtained by treating the pyrazolecarboxamideVa with P₂S₅ or Lawesson-reagent in a solvent like dioxane,tetrahydrofurane or toluene at a temperature between 0° C. and refluxtemperature, giving the pyrazolethioamide Vb and subsequent reaction ofthis pyrazolethioamide Vb with the boronic acid derivative of formula VIin the presence of a Pd-catalyst like Pd(P(phenyl)₃)₄, Pd(P(phenyl₃)Cl₂,PdCl₂dppb, Pd₂(dba)₃, Pd(OAc)₂, PdOAc₂/(o-tolyl)₃P, Pd(OAc)₂/dppf,Pd(PhCN)₂Cl/Ph₃As, Pd(CH₃CN)₂Cl₂, Pd₂(dba)₃/P(tert.butyl)₃,Pd(OAc)₂/P(tert.butyl)₂biphenyl, Pd(OAc)₂/TPPTS, Pd(OAc)₂/PCy₃,Pd(OAc)₂/P(O-i-Pr)₃, Pd(OAc)₂/2-dimethylamino-2′-dicyclohexylphosphinobiphenyl,Pd(OAc)₂/2-dimethylamino-2′-ditert.butylphosphinobiphenyl,Pd(OAc)₂/(o-biphenyl)P(cyclohexyl)₂ in a solvent like1,2-dimethoxyethane/water, DMF, DMA, THF/water, dioxane/water, benzene,toluene, xylene and others and a base like sodium carbonate, sodiumhydrogencarbonate, potassium carbonate, cesium carbonate, potassiumphosphate, triethylamine, sodium hydroxide, sodium ethylate, sodiumtert.butylate, silver oxide, barium carbonate, potassium fluoride orcesium fluoride at a temperature between 0° C. and reflux temperature.

The invention relates also to the compounds of the formulae Va and Vb,wherein R₁, R₂ and X have the meaning as defined for formula I and R₄ ishalogen, preferably chloro, bromo or iodo.

Compounds of formula IV are known from the literature or may be preparedfollowing the scheme 2.

The pyrazoles of formula II are known from the literature or may beprepared following the scheme 3.

Surprisingly, it has now been found that the novel compounds of formulaI have, for practical purposes, a very advantageous spectrum ofactivities for protecting plants against diseases that are caused byfungi as well as by bacteria and viruses.

The compounds of formula I can be used in the agricultural sector andrelated fields of use as active ingredients for controlling plant pests.The novel compounds are distinguished by excellent activity at low ratesof application, by being well tolerated by plants and by beingenvironmentally safe. They have very useful curative, preventive andsystemic properties and are used for protecting numerous cultivatedplants. The compounds of formula I can be used to inhibit or destroy thepests that occur on plants or parts of plants (fruit, blossoms, leaves,stems, tubers, roots) of different crops of useful plants, while at thesame time protecting also those parts of the plants that grow later e.g.from phytopathogenic microorganisms.

It is also possible to use compounds of formula I as dressing agents forthe treatment of plant propagation material, in particular of seeds(fruit, tubers, grains) and plant cuttings (e.g. rice), for theprotection against fungal infections as well as against phytopathogenicfungi occurring in the soil.

The compounds I are, for example, effective against the phytopathogenicfungi of the following classes: Fungi imperfecti (e.g. Botrytis,Pyricularia, Helminthosporium, Fusarium, Septoria, Cercospora andAlternaria) and Basidiomycetes (e.g. Rhizoctonia, Hemileia, Puccinia).Additionally, they are also effective against the Ascomycetes classes(e.g. Venturia and Erysiphe, Podosphaera, Monilinia, Uncinula) and ofthe Oomycetes classes (e.g. Phytophthora, Pythium, Plasmopara).Outstanding activity has been observed against powdery mildew (Erysiphespp.). Furthermore, the novel compounds of formula I are effectiveagainst phytopathogenic bacteria and viruses (e.g. against Xanthomonasspp, Pseudomonas spp, Erwinia amylovora as well as against the tobaccomosaic virus).

Within the scope of present invention, target crops to be protectedtypically comprise the following species of plants: cereal (wheat,barley, rye, oat, rice, maize, sorghum and related species); beet (sugarbeet and fodder beet); pomes, drupes and soft fruit (apples, pears,plums, peaches, almonds, cherries, strawberries, raspberries andblackberries); leguminous plants (beans, lentils, peas, soybeans); oilplants (rape, mustard, poppy, olives, sunflowers, coconut, castor oilplants, cocoa beans, groundnuts); cucumber plants (pumpkins, cucumbers,melons); fibre plants (cotton, flax, hemp, jute); citrus fruit (oranges,lemons, grapefruit, mandarins); vegetables (spinach, lettuce, asparagus,cabbages, carrots, onions, tomatoes, potatoes, paprika); lauraceae(avocado, cinnamomum, camphor) or plants such as tobacco, nuts, coffee,eggplants, sugar cane, tea, pepper, vines, hops, bananas and naturalrubber plants, as well as ornamentals.

The compounds of formula I are used in unmodified form or, preferably,together with the adjuvants conventionally employed in the art offormulation. To this end they are conveniently formulated in knownmanner to emulsifiable concentrates, coatable pastes, directly sprayableor dilutable solutions, dilute emulsions, wettable powders, solublepowders, dusts, granulates, and also encapsulations e.g. in polymericsubstances. As with the type of the compositions, the methods ofapplication, such as spraying, atomising, dusting, scattering, coatingor pouring, are chosen in accordance with the intended objectives andthe prevailing circumstances. The compositions may also contain furtheradjuvants such as stabilizers, antifoams, viscosity regulators, bindersor tackifiers as well as fertilizers, micronutrient donors or otherformulations for obtaining special effects.

Suitable carriers and adjuvants can be solid or liquid and aresubstances useful in formulation technology, e.g. natural or regeneratedmineral substances, solvents, dispersants, wetting agents, tackifiers,thickeners, binders or fertilizers. Such carriers are for exampledescribed in WO 97/33890.

The compounds of formula I are normally used in the form of compositionsand can be applied to the crop area or plant to be treated,simultaneously or in succession with further compounds. These furthercompounds can be e.g. fertilizers or micronutrient donors or otherpreparations which influence the growth of plants. They can also beselective herbicides as well as insecticides, fungicides, bactericides,nematicides, molluscicides or mixtures of several of these preparations,if desired together with further carriers, surfactants or applicationpromoting adjuvants customarily employed in the art of formulation.

The compounds of formula I can be mixed with other fungicides, resultingin some cases in unexpected synergistic activities.

Mixing components which are particularly preferred are azoles such asazaconazole, bitertanol, propiconazole, difenoconazole, diniconazole,cyproconazole, epoxiconazole, fluquinconazole, flusilazole, flutriafol,hexaconazole, imazalil, imibenconazole, ipconazole, tebuconazole,tetraconazole, fenbuconazole, metconazole, myclobutanil, perfurazoate,penconazole, bromuconazole, pyrifenox, prochloraz, triadimefon,triadimenol, triflumizole or triticonazole; pyrimidinyl carbinoles suchas ancymidol, fenarimol or nuarimol; 2-amino-pyrimidine such asbupirimate, dimethirimol or ethirimol; morpholines such as dodemorph,fenpropidin, fenpropimorph, spiroxamin or tridemorph; anilinopyrimidinessuch as cyprodinil, pyrimethanil or mepanipyrim; pyrroles such asfenpiclonil or fludioxonil; phenylamides such as benalaxyl, furalaxyl,metalaxyl, R-metalaxyl, ofurace or oxadixyl; benzimidazoles such asbenomyl, carbendazim, debacarb, fuberidazole or thiabendazole;dicarboximides such as chlozolinate, dichlozoline, iprodine,myclozoline, procymidone or vinclozolin; carboxamides such as carboxin,fenfuram, flutolanil, mepronil, oxycarboxin or thifluzamide; guanidinessuch as guazatine, dodine or iminoctadine; strobilurines such asazoxystrobin, kresoxim-methyl, metominostrobin, SSF-129, methyl2-[(2-trifluoromethyl)-pyrid-6-yloxymethyl]-3-methoxyacrylate or2-[α{[(α-methyl-3-trifluoromethyl-benzyl)imino]-oxy}-o-tolyl]-glyoxylicacid-methylester-O-methyloxime (trifloxystrobin); dithiocarbamates suchas ferbam, mancozeb, maneb, metiram, propineb, thiram, zineb or ziram;N-halomethylthio-dicarboximides such as captafol, captan, dichlofluanid,fluoromide, folpet or tolyfluanid; copper compounds such as Bordeauxmixture, copper hydroxide, copper oxychloride, copper sulfate, cuprousoxide, mancopper or oxine-copper; nitrophenol derivatives such asdinocap or nitrothal-isopropyl; organo phosphorous derivatives such asedifenphos, iprobenphos, isoprothiolane, phosdiphen, pyrazophos ortoclofos-methyl; and other compounds of diverse structures such asacibenzolar-S-methyl, anilazine, blasticidin-S, chinomethionat,chloroneb, chlorothalonil, cymoxanil, dichlone, diclomezine, dicloran,diethofencarb, dimethomorph, dithianon, etridiazole, famoxadone,fenamidone, fentin, ferimzone, fluazinam, flusulfamide, fenhexamid,fosetyl-aluminium, hymexazol, kasugamycin, methasulfocarb, pencycuron,phthalide, polyoxins, probenazole, propamocarb, pyroquilon, quinoxyfen,quintozene, sulfur, triazoxide, tricyclazole, triforine, validamycin,(S)-5-methyl-2-methylthio-5-phenyl-3-phenyl-amino-3,5-dihydroimidazol-4-one(RPA 407213),3,5-dichloro-N-(3-chloro-1-ethyl-1-methyl-2-oxopropyl)-4-methylbenzamide(RH 7281), N-allyl-4,5-dimethyl-2-trimethylsilylthiophene-3-carboxamide(MON 65500),4-chloro-4-cyano-N,N-dimethyl-5-p-tolylimidazole-1-sulfon-amide(IKF-916),N-(1-cyano-1,2-dimethylpropyl)-2-(2,4-dichlorophenoxy)-propionamide (AC382042), or iprovalicarb (SZX 722).

A preferred method of applying a compound of formula I, or anagrochemical composition which contains at least one of said compounds,is foliar application. The frequency of application and the rate ofapplication will depend on the risk of infestation by the correspondingpathogen. However, the compounds of formula I can also penetrate theplant through the roots via the soil (systemic action) by drenching thelocus of the plant with a liquid formulation, or by applying thecompounds in solid form to the soil, e.g. in granular form (soilapplication). In crops of water rice such granulates can be applied tothe flooded rice field. The compounds of formula I may also be appliedto seeds (coating) by impregnating the seeds or tubers either with aliquid formulation of the fungicide or coating them with a solidformulation.

The formulation, i.e. the compositions containing the compound offormula I and, if desired, a solid or liquid adjuvant, are prepared inknown manner, typically by intimately mixing and/or grinding thecompound with extenders, e.g. solvents, solid carriers and, optionally,surface active compounds (surfactants).

The agrochemical formulations will usually contain from 0.1 to 99% byweight, preferably from 0.1 to 95% by weight, of the compound of formulaI, 99.9 to 1% by weight, preferably 99.8 to 5% by weight, of a solid orliquid adjuvant, and from 0 to 25% by weight, preferably from 0.1 to 25%by weight, of a surfactant.

Advantageous rates of application are normally from 5 g to 2 kg ofactive ingredient (a.i.) per hectare (ha), preferably from 10 g to 1 kga.i./ha, most preferably from 20 g to 600 g a.i./ha. When used as seeddrenching agent, convenient dosages are from 10 mg to 1 g of activesubstance per kg of seeds.

Whereas it is preferred to formulate commercial products asconcentrates, the end user will normally use dilute formulations.

The following non-limiting Examples illustrate the above-describedinvention in more detail. Temperatures are given in degrees Celsius. Thefollowing abbreviations are used: m.p.=melting point; b.p.=boilingpoint. “NMR” means nuclear magnetic resonance spectrum. MS stands formass spectrum. “%” is percent by weight, unless correspondingconcentrations are indicated in other units.

EXAMPLE 1 1-Methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid(4′-chlorobiphenyl-2-yl) amide

A solution of 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid(0.68 g) and oxalyl chloride (0.49 g) in methylene chloride (30 ml) isstirred for 2 hours at room temperature in the presence of a catalyticamount of DMF. The resulting acid chloride solution is then added to asolution of 4′-chlorobiphenyl-2-ylamine (0.71 g) and triethylamine (0.36g) in 15 ml of methylene chloride at 0° C. The reaction mixture is thenstirred for 4 hours at room temperature. After distilling off thesolvent in a water-jet-vacuum, the residue is taken up inethylacetate/water. The ethylacetate phase is extracted twice withwater. After drying of the organic phase with Na₂SO₄, the solvent isdistilled off in a water-jet-vacuum and the residue purified by columnchromatography (silica gel; eluant: ethylacetate/hexane=1:1). 0.8 g of1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid(4′-chlorobiphenyl-2-yl) amide are obtained in the form of slightlybrownish crystals having a melting point of 144–146° C.

EXAMPLE 1 Suzuki-Coupling1-Methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid(4′-chlorobiphenyl-2-yl) amide

A solution of 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylicacid(2-bromo-phenyl)amide (0.64 g), 4-chlorobenzene boronic acid (0.29g), powdered sodium carbonate (0.25 g) and tetrakis(triphenylphosphine)palladium (0.04 g) in 25 ml 1,2-dimethoxyethane (DME) and 2 ml water isheated at reflux temperature for 20 hours. After cooling, the solvent isremoved in a water jet vacuum and the residue taken up inethylacetate/water. The ethylacetate phase is washed twice with waterand brine and then dried over sodium sulfate. Distilling off the solventleft the raw material which can be further purified by columnchromatography (silicagel; eluant: ethylacetate/hexane 1:1) orrecrystallization from TBME/hexane. The yield after purification is 0.6g; m.p.=145–146° C.

The following compounds of formula I are prepared in a similar way,using analogous methods.

TABLE 1 Compd. phys.data No. R₁ R₂ R₃ X m.p. ° C. 1 CH₃ CF₃ Cl O 144–1462 CH₃ CF₃ F O 149–151 3 CH₃ CF₃ Br O 4 CH₃ CF₃ I O 5 CH₃ CF₂H Cl O161–162 6 CH₃ CF₂H F O 144–145 7 CH₃ CF₂H Br O 8 CH₃ CF₂H I O 9 CF₃ CF₃Cl O 10 CF₃ CF₃ F O 11 CH₃ CFH₂ Cl O 12 CH₃ CFH₂ F O 13 CF₂H CF₃ F O 14CF₂H CF₃ Cl O 15 CFH₂ CF₃ F O 16 CFH₂ CF₃ Cl O 17 CH₃ CF₂CF₃ F O 146 18CH₂OCH₃ CF₃ Cl O 19 CH₂OCH₃ CF₃ F O 20 CH₂OCF₃ CF₃ Cl O 21 CH₂OCF₃ CF₃ FO 22 CH₃ CF₃ Cl S 85–86 23 CH₃ CF₃ F S 125–127 24 CH₃ CF₃ Br S 25 CH₃CF₃ I S 26 CH₃ CF₂H F S 27 CH₃ CF₂H Cl S 28 CH₃ CF₂H Br S 29 CH₃ CF₂H IS 30 CF₃ CF₃ Cl S 31 CF₃ CF₃ F S 32 CH₂OCH₃ CF₃ Cl S 33 CH₂OCH₃ CF₃ F S34 CH₂OCF₃ CF₃ Cl S 35 CH₂OCF₃ CF₃ F S 36 CH₃ CFH₂ Cl S 37 CH₃ CFH₂ F S38 CH₃ CF₂CF₃ F S

TABLE 2 [Va, Vb]

Compd. phys. data No. R₁ R₂ R₄ X m.p. ° C. 39 CH₃ CF₂H Cl O 40 CH₃ CF₂HBr O 41 CH₃ CF₂H F O 42 CH₃ CF₃ Cl O 120–121 43 CH₃ CF₃ Br O 127–128 44CH₃ CF₃ I O 176–177 45 CH₃ CF₃CF₂ Br O 46 CH₂OCH₃ CF₂H Cl O 47 CH₂OCH₃CF₂H Br O 48 CH₂OCH₃ CF₂H I O 49 CH₂OCH₃ CF₃ Cl O 50 CH₂OCH₃ CF₃ Br O 51CH₂OCH₃ CF₃ I O 52 CH₃ CF₂H Cl S 53 CH₃ CF₂H Br S 54 CH₃ CF₂H I S 55 CH₃CF₃ Cl S 107–108 56 CH₃ CF₃ Br S 109–110 57 CH₃ CF₃ I S 98–99 58 CH₃CF₃CF₂ Br S 102–103 59 CH₂OCH₃ CF₂H Cl S 60 CH₂OCH₃ CF₂H Br S 61 CH₂OCH₃CF₂H I S 62 CH₂OCH₃ CF₃ Cl S 63 CH₂OCH₃ CF₃ Br S 64 CH₂OCH₃ CF₃ I SFormulation Examples for Compounds of Formula I

Working procedures for preparing formulations of the compounds offormula I such as Emulsifiable concentrates, Solutions, Granulates,Dusts and Wettable powders are described in WO 97/33890.

Biological Examples: Fungicidal Actions

EXAMPLE B-1 Action against Puccinia Recondite/Wheat (Brownrust on Wheat)

1 week old wheat plants cv. Arina are treated with the formulated testcompound (0.02% active ingredient) in a spray chamber. One day afterapplication wheat plants are inoculated by spraying a spore suspension(1×10⁵ uredospores/ml) on the test plants. After an incubation period of2 days at 20° C. and 95% r. h. plants are kept in a greenhouse for 8days at 20° C. and 60% r.h. The disease incidence is assessed 10 daysafter inoculation. Compounds of Table 1 show good activity in this test(<20% infestation). Infestation is prevented virtually completely (0–5%infestation) with compounds 1, 2, 5, 6, 17, 22 and 23.

EXAMPLE B-2 Action against Podosphaera leucotricha/apple (Powdery mildewon apple)

5 week old apple seedlings cv. McIntosh are treated with the formulatedtest compound (0.002% active ingredient) in a spray chamber. One dayafter application apple plants are inoculated by shaking plants infectedwith apple powdery mildew above the test plants. After an incubationperiod of 12 days at 22° C. and 60% r. h. under a light regime of 14/10h (light/dark) the disease incidence is assessed.

Compounds of Table 1 show good activity in this test. The compounds 1,2, 5, 6, 17, 22 and 23 exhibit strong efficacy (<20% infestation).

EXAMPLE B-3 Action against Venturia inaequalis/apple (Scab on apple)

4 week old apple seedlings cv. McIntosh are treated with the formulatedtest compound (0.02% active ingredient) in a spray chamber. One dayafter application apple plants are inoculated by spraying a sporesuspension (4×10⁵ conidia/ml) on the test plants. After an incubationperiod of 4 days at 21° C. and 95% r. h. the plants are placed for 4days at 21° C. and 60% r. h. in a greenhouse. After another 4 dayincubation period at 21° C. and 95% r. h. the disease incidence isassessed.

Compounds of Table 1 show good activity in this test. The compounds 1,2, 5, 6, 17, 22 and 23 exhibit strong efficacy (<20% infestation).

EXAMPLE B-4 Action Against Erysiphe graminis/Barley (Powdery Mildew onBarley)

1 week old barley plants cv. Express are treated with the formulatedtest compound (0.02% active ingredient) in a spray chamber. One dayafter application barley plants are inoculated by shaking powdery mildewinfected plants above the test plants. After an incubation period of 6days at 20° C./18° C. (day/night) and 60% r. h. in a greenhouse thedisease incidence is assessed.

Compounds of Table 1 show good activity in this test. The compounds 1,2, 5, 6, 17, 22 and 23 exhibit strong efficacy (<20% infestation).

EXAMPLE B-5 Action Against Botrytis cinerea/Apple (Botrytis on AppleFruits)

In an apple fruit cv. Golden Delicious 3 holes are drilled and eachfilled with 30111 droplets of the formulated test compound (0.002%active ingredient). Two hours after application 501 of a sporesuspension of B. cinerea (4×10⁵ conidia/ml) are pipetted on theapplication sites. After an incubation period of 7 days at 22° C. in agrowth chamber the disease incidence is assessed.

Compounds of Table 1 show good activity in this test. The compounds 1,2, 5, 6, 17, 22 and 23 exhibit very strong efficacy (<10% infestation).

EXAMPLE B-6 Action Against Botrytis Cinerea/Grape (Botrytis on Grapes)

5 week old grape seedlings cv. Gutedel are treated with the formulatedtest compound (0.002% active ingredient) in a spray chamber. Two daysafter application grape plants are inoculated by spraying a sporesuspension (1×10⁵ conidia/ml) on the test plants. After an incubationperiod of 4 days at 21° C. and 95% r. h. in a greenhouse the diseaseincidence is assessed.

Compounds of Table 1 show good activity in this test. The compounds 1,2, 5, 6, 17, 22 and 23 exhibit very strong efficacy (<10% infestation).

EXAMPLE B-7 Action Against Botrytis cinerea/Tomato (Botrytis onTomatoes)

4 week old tomato plants cv. Roter Gnom are treated with the formulatedtest compound (0.002% active ingredient) in a spray chamber. Two daysafter application tomato plants are inoculated by spraying a sporesuspension (1×10⁵conidia/ml) on the test plants. After an incubationperiod of 4 days at 20° C. and 95% r. h. in a growth chamber the diseaseincidence is assessed.

Compounds of Table 1 show good activity in this test. The compounds 1,2, 5, 6, 17, 22 and 23 exhibit very strong efficacy (<10% infestation).

EXAMPLE B-8 Action Against Pyrenophora teres/Barley (Net Blotch onBarley)

1 week old barley plants cv. Express are treated with the formulatedtest compound (0.002% active ingredient) in a spray chamber. Two daysafter application barley plants are inoculated by spraying a sporesuspension (3×10⁴ conidia/ml) on the test plants. After an incubationperiod of 2 days at 20° C. and 95% r. h. plants are kept for 2 days at20° C. and 60% r.h. in a greenhouse. The disease incidence is assessed 4days after inoculation. Compounds of Table 1 show good activity in thistest. The compounds 1, 2, 5, 6, 17, 22 and 23 exhibit strong efficacy(<20% infestation).

EXAMPLE B-9 Action Against Septoria nodorum/Wheat (Septoria Leaf Spot onWheat)

1 week old wheat plants cv. Arina are treated with the formulated testcompound (0.02% active ingredient) in a spray chamber. One day afterapplication wheat plants are inoculated by spraying a spore suspension(5×10⁵ conidia/ml) on the test plants. After an incubation period of 1day at 20° C. and 95% r. h. plants are kept for 10 days at 20° C. and60% r.h. in a greenhouse. The disease incidence is assessed 11 daysafter inoculation. Compounds of Table 1 show good activity in this test.The compounds 1, 2, 5, 6, 17, 22 and 23 exhibit strong efficacy (<20%infestation).

1. A pyrazolecarboxamide of formula I

wherein X is sulfur; R₁ is C₁–C₃alkyl, C₁–C₃haloalkyl,C₁–C₃alkoxy-C₁–C₃alkyl or C₁–C₃haloalkoxy-C₁–C₃alkyl; R₂ isC₁–C₃haloalkyl; and R₃ is halogen.
 2. A compound of formula I accordingto claim 1, wherein R₁ is C₁–C₃alkyl; and R₃ is fluoro, chloro or bromo.3. A compound of formula I according to claim 1, wherein R₂ is CF₃,CF₂H, CFH₂, CF₂CF₃, CCl₃, CH₂CF₃, CH₂CCl₃ or CF₂CF₂CF₃.
 4. A compound offormula I according to claim 1, wherein R₁ is C₁–C₃haloalkyl; and R₃ isfluoro, chloro or bromo.
 5. A composition for controlling microorganismsand preventing attack and infestation of plants therewith, wherein theactive ingredient is a compound as claimed in claim 1 together with asuitable carrier.
 6. A method of controlling or preventing infestationof cultivated plants by phytopathogenic microorganisms by application ofa compound of formula I as claimed in claim 1 to plants, to partsthereof or the locus thereof.
 7. A process for the preparation of thecompounds according to claim 1, comprising: (A) reacting a pyrazolecarboxylic acid of the formula:

with an activating agent selected from the group consisting of thionylchloride, phosphorous pentachloride and oxalyl chloride thereby to forma a pyrazole carboxylic acid chloride of the formula:

(B) thereafter reacting said a pyrazole carboxylic acid chloride with anaromatic amine of the formula:

to form a pyrazolecarboxamide of the formula:

and (C) reacting the pyrazolecarboxamide with a phosphorpentasulfid orLawesson-reagent in a solvent selected from the group consisting ofdioxane, tetrahydrofurane, and toluene at a reaction temperature ofbetween about 0° C. and reflux temperature thereby to form the compoundsof formula I in claim 1; wherein: R₁ is C₁–C₃alkyl, C₁–C₃haloalkyl,C₁–C₃alkoxy-C₁–C₃alkyl or C₁–C₃haloalkoxy-C₁–C₃alkyl; R₂ isC₁–C₃haloalkyl; and R₃ is halogen.
 8. A process for the preparation ofthe compounds according to claim 1, comprising: (A) reacting a pyrazolecarboxylic acid chloride of the formula

with a substituted phenylamine of the formula:

in the presence of a first solvent and a first base thereby to form apyrazolecarboxamide of the formula:

(B) reacting the pyrazolecarboxamide with a phosphorpentasulfid orLawesson-reagent to form a pyrazolethioamide of the formula:

(C) reacting the pyrazolethioamide in the presence of a Pd-catalyst, asecond solvent, and a second base thereby to form the compounds offormula I in claim 1; and wherein: R₁ is C₁–C₃alkyl, C₁–C₃haloalkyl,C₁–C₃alkoxy-C₁–C₃alkyl or C₁–C₃haloalkoxy-C₁–C₃alkyl; R₂ isC₁–C₃haloalkyl; R₄ is chloro, bromo, or iodo.